6-Chloroindoline-2,3-dione → Rac-6-chloro-3-(3,5-dimethoxy-phenyl)-3-hydroxy-1,3-dihydro-indol-2-one

HRID 2102707Notes

Reaction equation

HRID 2102707 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([Mg]Br)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[Cl:13][C:14]1[CH:22]=[C:21]2[C:17]([C:18](=[O:24])[C:19](=[O:23])[NH:20]2)=[CH:16][CH:15]=1>O1CCCC1>[Cl:13][C:14]1[CH:22]=[C:21]2[C:17]([C:18]([C:5]3[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=3)([OH:24])[C:19](=[O:23])[NH:20]2)=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 2413316-Chloroindoline-2,3-dioneHCID 178493477HCID 178493477, compound

Product 1

HCID 57803060Rac-6-chloro-3-(3,5-dimethoxy-phenyl)-3-hydroxy-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-25 °C

Procedure

A solution of 3,5-dimethoxyphenyl magnesium bromide in tetrahydrofuran (1.0 M, 6.9 mmol) (Aldrich) was added dropwise with magnetic stirring to a suspension of 6-chloroisatin (0.5 g, 2.76 mmol) in tetrahydrofuran (14 mL) under argon with cooling in a −25° C. bath at such a rate that reaction temperature was kept below −10° C. Cooling bath was then removed and mixture was allowed to warm to room temperature. After stirring for an additional 2 hours, 15% aqueous ammonium chloride solution and water were added and mixture extracted with ethyl acetate. Ethyl acetate layers were then washed with water, brine, combined, dried (Na2SO4), filtered and concentrated. Residue was stirred in dichloromethane at room temperature for 15 minutes and filtered to give crude rac-6-chloro-3-(3,5-dimethoxy-phenyl)-3-hydroxy-1,3-dihydro-indol-2-one as an off-white powder. This was used in the next step without further purification.

Workup

  1. customthat reaction temperature
  2. customwas kept below −10° C
  3. temperatureCooling bath
  4. customwas then removed
  5. temperatureto warm to room temperature
  6. addition15% aqueous ammonium chloride solution and water were added
  7. extractionmixture extracted with ethyl acetate
  8. washEthyl acetate layers were then washed with water, brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. stirringResidue was stirred in dichloromethane at room temperature for 15 minutes
  13. filtrationfiltered

Sources & evidence

ORD record
ord-0e1b8f544eea48b59acd86591cc5141b
Source dataset
uspto-grants-2009_08
Patent number
US07576082B2

Reaction notes

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